title: Evolutionary computation for discovery of composite transcription factor binding sites.
abstract: Previous research demonstrated the use of evolutionary computation for the discovery of transcription factor binding sites (TFBS) in promoter regions upstream of coexpressed genes. However, it remained unclear whether or not composite TFBS elements, commonly found in higher organisms where two or more TFBSs form functional complexes, could also be identified by using this approach. Here, we present an important refinement of our previous algorithm and test the identification of composite elements using NFAT/AP-1 as an example. We demonstrate that by using appropriate existing parameters such as window size, novel-scoring methods such as central bonusing and methods of self-adaptation to automatically adjust the variation operators during the evolutionary search, TFBSs of different sizes and complexity can be identified as top solutions. Some of these solutions have known experimental relationships with NFAT/AP-1. We also indicate that even after properly tuning the model parameters, the choice of the appropriate window size has a significant effect on algorithm performance. We believe that this improved algorithm will greatly augment TFBS discovery.
authors.affiliation: Natural Selection, Inc, San Diego, CA 92121, USA.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Fogel
authors.forename: V William
authors.initials: VW
authors.lastname: Porto
authors.forename: Gabor
authors.initials: G
authors.lastname: Varga
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Dow
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Craven
authors.forename: David M
authors.initials: DM
authors.lastname: Powers
authors.forename: Harry B
authors.initials: HB
authors.lastname: Harlow
authors.forename: Eric W
authors.initials: EW
authors.lastname: Su
authors.forename: Jude E
authors.initials: JE
authors.lastname: Onyia
authors.forename: Chen
authors.initials: C
authors.lastname: Su
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology; D019143:Evolution, Molecular; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D050778:NFATC Transcription Factors; D050811:Octamer Transcription Factor-1; D018808:Transcription Factor AP-1; D014157:Transcription Factors